The objectives of this research proposal are to examine the developmental changes in some aspects of renal function during late gestation and after birth. Renal oxygen consumption and uptake of glucose, lactate and free fatty acids will be related to renal functions such as sodium transport and acid-base regulation. The effects of acute hypoxemia, metabolic acidemia, and infusion of hormones such as vasopressin, angiotensin and catecholamines on these functions will be assessed. The possible role of the kidney in providing energy substrate to the body, by glycogenolysis or gluconeogenesis will be studied in fetal and newborn lambs under conditions of hypoxemia, acidemia or stimulation by epinephrine. We will measure rates of renin secretion in response to hormone infusion, acute hypoxemia, bilateral carotid occlusion, reduction in circulating blood volume or reduction in renal blood flow. These studies will be performed in chronically-instrumented fetal and neonatal lambs. We have perfected a technique by which a small catheter is inserted into the left renal vein in these lambs. This catheter does not modify renal blood flow and it permits repeated sampling substrates and renin can be measured. Renal blood flow can be measured repeatedly by the radionuclide-labelled microsphere method. Knowing this and arteriovenous concentration difference, it is possible by application of the Fick method to estimate uptake or release of many substances by the kidney. A chronically-implanted bladder catheter in the lambs provides for collection of urine to measure urinary excretion rates and concentrations of electrolytes. The importance and uniqueness of this project lies in our ability to make repeated, quantitative measurements of renal function and metabolism in the fetus and neonate in the absence of the effects of anesthesia and acute surgery; it will provide information on changes in the metabolic role of the kidney after birth and the role of the kidney during stress responses. The information will greatly expand our knowledge of the physiology of the kidney during the perinatal period and will provide the basis upon which therapeutic management of the infant can be based.